tailieunhanh - Báo cáo khoa học: Tumor necrosis factor-a-induced caspase-1 gene expression

Tumour necrosis factor-a(TNF-a) is a cytokine that is involved in many functions, including the inflammatory response, immunity and apoptosis. Some of the responses of TNF-a are mediated by caspase-1, which is involved in the production of the pro-inflammatory cytokines interleukin-1b, interleukin-18 and interleukin-33. | ễFEBS Journal Tumor necrosis factor-a-induced caspase-1 gene expression Role of p73 Nishant Jain Ch Sudhakar and Ghanshyam Swarup Centre for Cellular and Molecular Biology Hyderabad India Keywords caspase-1 caspase-5 IRF-1 p73 TNF-a Correspondence G. Swarup Centre for Cellular and Molecular Biology UppalRoad Hyderabad-500 007 India Fax 91 40 27160591 91 40 27160311 Tel 91 40 27192616 91 40 27160222 E-mail gshyam@ Received 2 May 2007 revised 15 June 2007 accepted 2 July 2007 doi Tumour necrosis factor-a TNF-a is a cytokine that is involved in many functions including the inflammatory response immunity and apoptosis. Some of the responses of TNF-a are mediated by caspase-1 which is involved in the production of the pro-inflammatory cytokines interleukin-1b interleukin-18 and interleukin-33. The molecular mechanisms involved in TNF-a-induced caspase-1 gene expression remain poorly defined despite the fact that signaling by TNF-a has been well studied. The present study was undertaken to investigate the mechanisms involved in the induction of caspase-1 gene expression by TNF-a. Treatment of A549 cells with TNF-a resulted in an increase in caspase-1 mRNA and protein expression which was preceded by an increase in interferon regulatory factor-1 and p73 protein levels. Caspase-1 promoter reporter was activated by the treatment of cells with TNF-a. Mutation of the interferon regulatory factor-1 binding site resulted in the almost complete loss of basal as well as of TNF-a-induced caspase-1 promoter activity. Mutation of the p53 p73 responsive site resulted in reduced TNF-a-induced promoter activity. Blocking of p73 function by a dominant negative mutant or by a p73-directed small hairpin RNA reduced basal as well as TNF-a-induced caspase-1 promoter activity. TNF-a-induced caspase-1 mRNA and protein levels were reduced when p73 mRNA was down-regulated by small hairpin RNA. Caspase-5 gene expression was induced by TNF-a which was .